Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5443_Библиотеки_им_академика_М_И_Перельмана
.pdf
Viscosity: HPMC solutions exhibit a certain level of viscosity. This viscosity can en-
hance the residence time of drug formulations or other products on mucosal surfaces,
ensuring prolonged contact.
Controlled release: HPMC can be used to c ontrol the release of drugs or other active
ingredients by forming a gel-like matrix that slows down the diffusion of subs tances
through it. This can lead to sustained drug release in the mucosal area.
Ease of formulation: HPMC is available in various grades with different viscosities,
making it versatile for formulating products like oral tablets, buccal films, eye drops,
and vaginal gels, among others.
Common applications of HPMC as a mucoadhesive polymer include:
– Oral drug delivery: HPMC can be used in oral drug formulations to improve drug
absorption, and prolong drug residence time in the gastrointestinal tract.
– Ophthalmic products: In eye drops and ointments, HPMC can enhance the reten-
tion of the medication on the ocular surface.
– Buccal and sublingual delivery: HPMC-based films or tablets can be used for buc-
cal and sublingual drug delivery, where the drug is held in contact with the oral
mucosa for absorption [21].
– Vaginal drug delivery: HPMC gels or creams are used for localized drug delivery
to the vaginal mucosa.
– Nasal drug delivery: HPMC can be incorporated into nasal sprays or gels for im-
proved drug retention and absorption through the nasal mucosa.
7.3.3 Chitosan
Chitosan is a natural polymer derived from chitin, found in the exoskeletons of crus-
taceans. It has strong mucoadhesive properties and is used in various mucosal drug
delivery systems. Chitosan is another mucoadhesive polymer commonly used in phar-
maceutical and biomedical applications [22]. Chitosan is derived from chitin, a natural
biopolymer found in the shells of crustaceans like shrimp and crabs. It has gained
popularity due to its biocompatibility, biodegradability, and mucoadhesive properties.
Here is how chitosan serves as a mucoadhesive polymer:
Mucoadhesion: Chitosan has a strong positive charge, which allows it to interact with
negatively charged mucous membranes in the body. This electrostatic interaction facil-
itates the adhesion of chitosan-based formulations to mucosal surfaces.
Biocompatibility: Chitosan is generally considered safe and well-tolerated by the
human body [23]. It does not typically cause significant irritation or adverse reactions
when applied to mucous membranes.
7 Virtual screening of mucoadhesive polymers 133
https://t.me/med1917
Bioadhesive strength: Chitosan exhibits a high degree of bioadhesive strength, mean-
ing it can adhere to mucosal surfaces for an extended period. This property is crucial
for maintaining contact between drug formulations and mucosal tissues.
Controlled release: Chitosan can be used to control release of drugs or other active in-
gredients. It forms a gel-like matrix when hydrated, which can slow down the diffusion
of substances and lead to sustained release [23].
Enhanced drug absorption: When chitosan-based formulations are applied to mucosal
surfaces, they can improve the absorption of drugs or other compounds, making them
more bioavailable [24].
Common applications of chitosan as a mucoadhesive polymer include:
– Oral drug delivery: Chitosan can be used in oral drug formulations to improve
drug absorption and prolong drug residence time in the gastrointestinal tract.
– Nasal drug delivery: Chitosan can be incorporated into nasal sprays, gels, or pow-
ders to enhance drug absorption through the nasal mucosa.
– Buccal and sublingual delivery: Chitosan-based films or tablets can be used for
buccal and sublingual drug delivery, where the drug is held in contact with the
oral mucosa for absorption [22].
– Vaginal drug delivery: Chitosan gels or suppositories are used for localized drug
delivery to the vaginal mucosa.
– Wound dressings: Chitosan has also been used in wound dressings and bandages
due to its ability to adhere to wound surfaces and promote tissue regeneration.
7.3.4 Polyvinylpyrrolidone (PVP)
Polyvinylpyrrolidone (PVP) is a synthetic polymer that can be used in mucoadhesive
drug delivery systems, especially in oral formulations. PVP, also known as polyvidone
or povidone, is a water-soluble polymer that is often used in pharmaceuticals and var-
ious other applications. It has been employed as a mucoadhesive polymer due to its
unique properties [24]. Mucoadhesion refers to the ability of a material to adhere to
mucosal surfaces, such as those found in the gastrointestinal tract, respiratory tract,
or even the eyes. Here is how PVP can function as a mucoadhesive polymer:
Hydrophilicity: PVP is highly hydrophilic, which means it has a strong affinity for
water. Mucosal surfaces in the body are moist and contain a layer of mucus, which is
primarily composed of water. PVP’s hydrophilic nature allows it to readily interact
with this mucus layer [24].
134 Gowtham Menon et al.
https://t.me/med1917
Adhesive properties: PVP molecules can form hydrogen bonds with the glycoproteins
present in mucus. This interaction helps PVP adhere to mucosal surfaces, promoting
prolonged contact between the material and the mucosa [25].
Bioavailability enhancement: When PVP is used as a mucoadhesive in pharmaceutical
formulations (e.g., tablets, films, or gels), it can improve the bioavailability of drugs.
By adhering to mucosal surfaces, it can prolong the release of the active pharmaceuti-
cal ingredient (API) and increase its absorption through the mucosa, leading to more
efficient drug delivery [26].
Reduced irritation: In topical formulations, PVP’s mucoadhesive properties can help
reduce irritation and washout of the product, increasing its effectiveness and patient
comfort.
Controlled drug release: PVP can be used to control the release rate of drugs by adjust-
ing the concentration and molecular weight of the polymer [26]. This controlled release
is especially useful for drugs that need to be delivered slowly over an extended period.
Compatibility: PVP is generally considered safe and well-tolerated by the body, mak-
ing it suitable for use in various medical and pharmaceutical applications.
Biodegradability: PVP is biodegradable, which means it can break down naturally
over time without causing harm to the body.
7.3.5 Polyethylene oxide (PEO)
Polyethylene oxide (PEO) is a hydrophilic polymer that is widely used in pharmaceutical
formulations as a mucoadhesive polymer. Mucoadhesion is the ability of a polymer to ad-
here to the mucus layer that lines the mucosal membranes of the body, such as the oral,
nasal, and gastrointestinal tracts [27]. PEO is a good mucoadhesive polymer because it is
hydrophilic and has a flexible chain structure. This allows it to interact with the mucin
glycoproteins in the mucus layer and form strong bonds. PEO is mucoadhesive to a variety
of mucosal surfaces, including the oral, nasal, and gastrointestinal tracts [28]. It is also bio-
compatible and nontoxic, which makes it a safe material to use in drug delivery systems.
PEO can be used in a variety of mucoadhesive drug delivery systems, including:
Buccal patches, for the delivery of drugs to the systemic circulation via the buccal
mucosa
Nasal sprays, for the delivery of drugs to the systemic circulation or the local
nasal mucosa [28]
Gastro retentive tablets, for the extended release of drugs in the stomach
Rectal and vaginal suppositories, for the delivery of drugs to the local mucosa or
the systemic circulation
7 Virtual screening of mucoadhesive polymers 135
https://t.me/med1917
In addition to its mucoadhesive properties, PEO also has several other desirable prop-
erties for pharmaceutical formulations, including [29]:
– It is soluble in water and other polar solvents.
– It is nontoxic and biocompatible.
– It is stable to a wide range of pH and temperature conditions.
– It is relatively inexpensive and easy to process.
7.3.6 Sodium alginate
Sodium alginate (SA) is a natural polymer derived from seaweed. It can be used in
mucoadhesive formul ations, especially in the context of gastrointestinal drug deliv-
ery. SA is a natural polysaccharide that is derived from brown algae. It is a linear
polymer composed of alternating blocks of β-
D-mannuronic acid and α-L-guluronic
acid [30]. SA is a biocompatible and nontoxic material, which makes it a safe material
to use in drug delivery systems.
SA is a good mucoadhesive polymer because it has several desirable properties,
including:
– It is a hydrophilic polymer, which means that it interacts well with the mucin gly-
coproteins in the mucus layer.
– It is a viscous polymer, which helps it to adhere to the mucus layer.
– It can be gelled in the presence of divalent cations, such as calcium ions. This al-
lows it to form a strong adhesive bond with the mucus layer.
SA is mucoadhesive to a variety of mucosal surfaces, including the oral, nasal, and
gastrointestinal tracts [30]. It is also biocompatible and nontoxic, which makes it a
safe material to use in drug delivery systems.
SA can be used in a variety of mucoadhesive drug delivery systems, including:
Buccal patches, for the delivery of drugs to the systemic circulation via the buccal
mucosa
Nasal sprays, for the delivery of drugs to the systemic circulation or the local
nasal mucosa
Gastro retentive tablets, for the extended release of drugs in the stomach
Rectal and vaginal suppositories, for the delivery of drugs to the local mucosa or
the systemic circulation
In addition to its mucoadhesive properties, SA also has several other desirable proper-
ties for pharmaceutical formulations, including:
– It is biodegradable and biocompatible.
– It is nontoxic and nonirritating.
– It is stable to a wide range of pH and temperature conditions.
– It is relatively inexpensive and easy to process.
136 Gowtham Menon et al.
https://t.me/med1917
7.3.7 Polycarbophil
Polycarbophil is indeed a mucoadhesive polymer commonly used in pharmaceutical
and medical applications [31]. Mucoadhesive polymers are substances that can adhere
to the mucus layer that lines various mucous membranes in the body, such as those
found in the gastrointestinal tract, nasal passages, and vaginal walls. This property is
beneficial for several reasons:
Drug delivery: Polycarbophil is often used as a drug delivery system because of its
mucoadhesive properties. When incorporated into formulations, it can help drugs ad-
here to mucosal surfaces for an extended period, allowing for controlled and sus-
tained release of medications. This is especially useful for drugs that need to be
slowly absorbed or localized in specific areas.
Enhanced bioavailability: Mucoadhesive polymers like polycarbophil can improve the
bioavailability of certain drugs by increasing their contact time with the mucosal sur-
faces. This can lead to better absorption and therapeutic outcomes.
Reduced side effects: By keeping drugs in contact with the mucosal surface, mucoad-
hesive polymers can reduce systemic exposure and potential side effects, which can
be particularly important for drugs with a narrow therapeutic window [31].
Improved formulations: Polycarbophil can be used in various formulations such as gels,
tablets, and patches to improve the ease of administration and patient compliance.
Vaginal and rectal applications: Polycarbophil-based formulations are often used in
vaginal gels and rectal suppositories for drug delivery and to enhance the retention of
medications at these mucosal sites.
Gastrointestinal use: In the gastrointestinal tract, polycarbophil can be used in tablet
formulations to enhance the retention of drugs in the stomach or intestines, which
can be beneficial for drugs that need to act locally within the gastrointestinal system.
Polycarbophil works by forming hydrogen bonds and other interactions with the muco-
sal surfaces, creating a strong adhesive bond. This helps keep the drug or formulation
in close contact with the mucosa for an extended period, improving its therapeutic
effectiveness.
7.3.8 Sodium hyaluronate
Sodium hyaluronate is a natural polymer found in the body, particularly in the eyes
and joints. Sodium hyaluronate is another example of a mucoadhesive polymer used
in various pharmaceutical and medical applications [32]. Hyaluronic acid, the parent
7 Virtual screening of mucoadhesive polymers 137
https://t.me/med1917
compound of sodium hyaluronate, is a naturally occurring polysaccharide found in
the extracellular matrix of connective tissues, synovial fluid, and the vitreous humor
of the eye. It is known for its high water-binding capacity and viscoelastic properties,
making it a valuable substance in medical and cosmetic fields [33].
Here is how sodium hyaluronate functions as a mucoadhesive polymer:
Mucosal adhesion: Sodium hyaluronate can adhere to mucosal surfaces, such as those
in the eyes, nose, mouth, and vaginal walls, due to its mucoadhesive properties. This
adhesion is mainly attributed to the interaction of hyaluronic acid with mucin, a key
component of mucus [33].
Viscoelasticity: Sodium hyaluronate has a high molecular weight, which contributes
to its viscoelastic nature. This property allows it to create a protective, lubricating
film on mucosal surfaces, improving comfort and reducing irritation. In ophthalmol-
ogy, for example, it is used as eye drops to provide relief for dry eyes.
Drug delivery: Sodium hyalur onate can be used as a drug delivery system, particu-
larly in ophthalmology. Eye drops or gels containing sodium hyaluronate can enhance
drug retention on the ocular surface, increasing the therapeutic effect and reducing
the need for frequent administration.
Wound healing: In wound care, sodium hyaluronate is used as a mucoadhesive dress-
ing to cover and protect wounds, including chronic ulcers [34]. It helps maintain a
moist environment for wound healing and adheres well to the wound bed.
Orthopedics: In orthopedic surgery, sodium hyaluronate is used as a viscosupplement
for the treatment of osteoarthritis. It is injected into the synovial joints to improve
joint lubrication and reduce pain.
Dermal fillers: In cosmetic medicine, sodium hyaluronate is used as a dermal filler to
add volume to the skin and reduce the appearance of wrinkles. It can adhere to the
dermal tissue, providing long-lasting results.
Sodium hyaluronate is well-tolerated and considered safe for medical and cosmetic
applications. However, like any medi cal intervention, it should be administered by
qualified healthcare professionals to ensure proper dosing and minimize the risk of
complications [35]. The use of sodium hyaluronate as a mucoadhesive polymer is ver-
satile and continues to expand as new applications are explored in the field of drug
delivery and tissue engineering.
138 Gowtham Menon et al.
https://t.me/med1917
7.3.9 Pectin
Pectin is a natural mucoadhesive polymer commonly used in various pharmaceutical,
food, and cosmetic applications. It is primarily extracted from citrus fruits, apples,
and other plant sources [35]. Pectin is a complex polysaccharide with unique proper-
ties that make it suitable for mucoadhesive applications:
Mucosal adhesion: Pectin can adhere to mucosal surfaces due to its charged func-
tional groups. It can form hydrogen bonds and electrostatic interactions with mucins
and other molecules on the mucosal lining. This adhesive property allows pectin to
stay in contact with mucosal membranes [36].
Drug delivery: Pectin can be used as a mucoadhesive in drug delivery systems. It is
often incorporated into oral tablets, patches, or gels to improve the retention of drugs
in the gastrointestinal tract. Pectin-based drug delivery systems can enhance drug ab-
sorption, reduce side effects, and prolong drug release.
Gastrointestinal applications: Pectin is used in oral formulations to control drug re-
lease in the stomach and intestines. Adhering to the mucosal lining can prolong drug
residence time , making it suitable for drugs that need to be released slowly or tar-
geted to specific areas of the gastrointestinal tract.
Vaginal applications: Pectin can also be utilized in vaginal formulations, such as gels
or suppositories [35]. In this context, it helps maintain contact with the vaginal mu-
cosa, making it effective for drug delivery, contraception, or the treatment of vaginal
infections.
Wound dressings: Pectin-based wound dressings are used to cover and protect vari-
ous types of wounds, including burns, ulcers, and surgical incisions. These dressings
adhere to the wound bed, create a moist environment, and promote wound healing.
Cosmetic and personal care products: Pectin is used in cosmetic and personal care
products, such as creams, lotions, and shampoos [37]. Its mucoadhesive properties
allow these products to adhere to the skin or hair, enhancing their efficacy and pro-
viding longer-lasting effects.
Food industry: In the food industry, pectin is used as a gelling agent and thickener in
jams, jellies, and fruit preserves.
7.3.10 Gellan gum
Gellan gum is a versatile biopolymer that has been studied and used in various phar-
maceutical and biomedical applications, including as a mucoadhesive polymer. Mu-
coadhesive polymers are substances that adhere to mucosal surfaces, such as those
7 Virtual screening of mucoadhesive polymers 139
https://t.me/med1917
found in the gastrointestinal tract or the oral cavity. Gellan gum has several proper-
ties that make it suitable for this purpose:
Biocompatibility: Gellan gum is derived from microbial fermentation, making it a nat-
ural and biocompatible material. It is generally recognized as safe by the U.S. Food
and Drug Administration (FDA), which means it is safe for consumption [38].
Gel-forming properties: Gellan gum can form gels in the presence of cations (such as
calcium or magnesium ions). This gel-forming ability allows it to interact with muco-
sal surfaces and adhere to them, prolonging the contact time between the drug or
therapeutic agent and the mucosa.
Tunable adhesive strength: The adhesive strength of gellan gum can be adjusted by
altering the formulation, concentration, and cross-linking agents. This flexibility al-
lows for customization to suit specific mucoadhesive applications [38].
Sustained drug release: Gellan gum can encapsulate drugs or therapeutic agents
within its gel matrix [39]. The mucoadhesive nature of gellan gum can slow down the
release of these substances, making it a suitable candidate for controlled drug deliv-
ery systems.
High water-holding capacity: Gellan gum can retain significant amount of water,
which can help maint ain the hydration of mucosal tissues [40]. This property is im-
portant for mucosal health and comfort.
Compatibility with active ingredients: Gellan gum is compatible with a wide range of
APIs, and it does not interfere with their stability or efficacy.
Ease of processing: Gellan gum can be easily processed into various dosage forms, in-
cluding as tablets, films, gels, and liquid formulations, making it adaptable to different
administration routes.
Gellan gum has been investigated for various mucoadhesive applications, such as buc-
cal drug delivery (for medications that are absorbed through the oral mucosa), gastro-
intestinal drug delivery (for drugs that require prolonged contact with the stomach or
intestines), and wound care (for promoting the adhesion of dressings to skin or muco-
sal wounds) [40].
The ability of scientists to gather, retrieve, and evaluate information, as well as
conduct “virtual” experiments, has been greatly enhanced by computers. A “quiet ex-
plosion” in contemporary polymer discovery has recently been brought on by com-
puter-based polymer design. By using molecular modeling, theoretical computation,
and prediction techniques, computer-based polymer design can direct and aid in the
design of new therapeutic polymers with desired features [41]. The goal of employing
computers in polymer design is to examine how the polymer interacts with its recep-
tor site and “design” molecules that fit the receptor site best. The fundamental prem-
140 Gowtham Menon et al.
https://t.me/med1917
ise is that structural and chemical complementarities to the target receptor produce a
good match [42].
7.4 Computational techniques in pharma
Computational techniques play a crucial role in the pharmaceutical industry, aiding
in drug discovery, development, and various aspects of research and development.
Here are some key computational techniques used in the pharmaceutical field:
1. Molecular docking: Molecular docking is a widely used technique for predicting
how small molecules (drugs or potential drug candidates) interact with specific
target proteins or receptors. It helps in identifying potential binding modes, bind-
ing affinities, and the likelihood of a compound binding to a target [43].
2. Quantitative structure–activity relationship (QSAR) analysis: QSAR models
correlate the chemical structure and physicochemical proper ties of compounds
with their biological activities [43]. QSAR models help in predicting the biological
activity of new compounds before synthesis or testing.
3. Pharmacophore modeling: Pharmacophores are abstract representations of mo-
lecular features that are essential for a molecule’ s interaction with a biological
target [44]. Pharmacophore modeling helps in identifying key interactions re-
quired for binding and designing new compounds based on these features.
4. Machine learning (ML) and artificial intelligence (AI): ML algorithms and AI
are used to analyze large datasets, predict drug–target interactions, optimize
drug candidates, and identify potential drug repurposing opportunities [45].
These techniques can also aid in virtual screening (VS) and lead optimization.
5. Quantum mechanics (QM) and molecular dynamics (MD) simulations:QM
simulations provide detailed insights into the electronic structure and properties
of molecules [45]. MD simulations are used to study the behavior of molecules
over time, providing information about their conformational changes and inter-
actions with their environment [46].
6. Chemoinformatics: Chemoinformatics involves the use of computational techni-
ques to analyze and manage chemical data [46]. It includes methods for chemical
database searching, compound library design, and chemical property prediction.
7. Network pharmacology: This approach integrates network analysis, computa-
tional biology, and systems biology to study complex interactions between drugs,
targets, and diseases [47]. It helps in understanding the polypharmacology of
drugs and their effects on biological networks.
8. In silico toxicology: Computational tools are used to predict the potential toxicity
of drug candidates, which is essential for regulatory approval and safety assess-
ment [47, 48].
7 Virtual screening of mucoadhesive polymers 141
https://t.me/med1917
9. Homology modeling: When experimental structures of target proteins are not
available, homology modeling (comparative modeling) is used to predict their
three-dimensional structures, based on known homologous structures [49].
10. Chemical informatics and data mining: These techniques involve the extraction
of valuable information from chemical and biological data sources, aiding in the
identification of potential drug targets, compound libraries, and biomarker dis-
covery [50].
11. Structure-based drug design (SBDD): SBDD relies on the three-dimensional
structures of biological targets to design molecules that specifically interact with
the target [50]. It often involves molecular docking, VS, and de novo drug design.
These computational techniques have revolutionized the pharmaceutical industry by
accelerating drug discovery, reducing costs, and increasing the efficiency of the drug
development process [51]. They are often used in conjunction with experimental ap-
proaches to design, optimize, and bring new drugs to market more rapidly and safely.
An innovative method known as VS, sometimes known as in silico screening, is
gaining popularity in the pharmaceutical industry as a successful and economical tool
for finding new lead compounds [52]. The principles involved – the computational
analysis of chemical databases to identify compounds appropriate for a specific bio-
logical receptor – have been studied for several years in molecular modeling groups,
but the availability of affordable high-performance computing platforms has revolu-
tionized the procedure and allowed increasingly complex and accurate analyses to be
carried out on very detailed and pertinent bases for prioritizing compounds for bio-
logical screening [53]. To find novel leads and reagents for pharmaceutical research,
VS offers a useful method.
7.5 Virtual screening of mucoadhesive polymers
VS is a computational technique widely used in drug discovery and materials science
to identify potential drug candidates or materi als with the desired properties from
large databases of compounds or structures [54]. It involves the use of computer algo-
rithms and simulations to predict the likelihood that a given molecule or material will
have a specific biological activity or property of interest, such as binding to a target
protein, inhibiting an enzyme, or possessing certain physical or chemical proper-
ties [53].
Here are the key steps and components of VS of mucoadhesive polymers:
142 Gowtham Menon et al.
https://t.me/med1917
Соседние файлы в папке Библиотека им академика М.И. Перельмана